The Falcons led right up until the fourth minute of stoppage time, but saw their slender lead converted into an even more slender defeat by a Mark Mapletoft penalty goal at the death.
Newcastle – at present the only English side guaranteed a place in next season's Heineken Cup thanks to their victory in the Powergen Cup – came back from an early Barry Everitt penalty to hand debutant Matthew Tate a scintillating try with his first touch of the ball.
Newcastle ran out of defence with Tom May finding Michael in support Stephenson. The fullback surged into the Irish half before delivering a perfect pass to Tate, who skinned Michael Horak to score under the posts.
The superb try lifted the Falcons and Hall Charlton soon found May on the wing who sent Stuart Grimes charging through the started visitors. The Scotland lock then pulled off a wonderful reverse pass for Warren Britz to score.
Then the Falcons were rather lucky to survive a breakaway by Nick Kennedy and it needed a big tackle from May to drive him into touch five metres out.
Dave Walder kicked an early second-half penalty to put his side into a health 15-6 lead, but when the Falcons had flanker Warren Britz sin-binned for going over the ball, they were under immediate pressure.
Exiles' winger Paul Sackey looked like he had narrowed the gap by scoring from a quickly-taken penalty, but referee Wayne Barnes ruled that Sackey had made a double movement in the act of dotting down.
The Irish got over the line with just four minutes of normal time left when Neal Hatley scrambled over and Mark Mapletoft converted to make it 15-13.
With a minute to go, Grimes thundered down the right and May just could not hold his pass with the line beckoning.
It proved a costly miss with Mapletoft kicking an 84th-minute penalty to give Irish the lead for the first time in the match and they hung on for an unlikely win.
For Newcastle Falcons:Tries: Tate, Britz Con: Walder Pen: Walder
For London Irish:Tries: Hatley Con: Mapletoft Pens: Everitt 2, Mapletoft